Abstract
Cell migration is fundamental to the development and physiological maintenance of organisms. Studying how cell migration is regulated is critical to the understanding of several developmental disorders, and it may help develop novel therapeutic approaches to disease conditions caused by erroneous cell migration, such as metastatic tumors. In the C. elegans nematode, the two specialized distal tip cells (DTCs) migrate long distances during nematode development, and therefore provide an in vivo model system for the study of developmentally regulated cell migration. We identified cacn-1/cactin, a well-conserved, novel regulator of cell migration in a genome-wide RNAi screen for regulators of DTC migration. RNAi depletion experiments and analysis of the hypomorphic allele cacn-1(tm3126) indicate that CACN-1 is required during DTC migration for proper pathfinding and for cessation of DTC migration at the end of larval morphogenesis. Strong expression of CACN-1 in the DTCs, and data from cell-specific RNAi depletion experiments, suggest that CACN-1 is required cell-autonomously to control DTC migration. Importantly, genetic interaction data with Rac GTPase activators and effectors suggest that CACN-1 acts in the mig-2/Rac pathway, and possibly in parallel to ced-10/Rac, to control DTC pathfinding. Rac reporter strain observations, as well as real-time PCR and transcriptome sequencing results, indicate that CACN-1 does not control the Rac GTPase pathway transcriptionally. Analysis of Rac GTPase protein levels in cacn-1 RNAi treated animals suggests that cacn-1 does not regulate MIG-2 or CED-10 protein levels. Our Rac activation assay study, on the other hand, shows increased levels of active MIG-2 and CED-10 Rac GTPases as a result of cacn-1 loss. These results suggest that cacn-1 is required for negative regulation of Rac GTPase activity, thereby allowing the proper level of Rac activation required for normal DTC migration.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
